Life Sciences, Burnet Institute, Melbourne, VIC 3004, Australia.
Department of Immunology, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
Cell Rep Med. 2020 Dec 22;1(9):100157. doi: 10.1016/j.xcrm.2020.100157.
CD4 T follicular helper cells (Tfh) are key drivers of antibody development. During malaria in children, the activation of Tfh is restricted to the Th1 subset and not associated with antibody levels. To identify Tfh subsets that are associated with antibody development in malaria, we assess Tfh and antibodies longitudinally in human volunteers with experimental infection. Tfh cells activate during infection, with distinct dynamics in different Tfh subsets. Th2-Tfh cells activate early, during peak infection, while Th1-Tfh cells activate 1 week after peak infection and treatment. Th2-Tfh cell activation is associated with the functional breadth and magnitude of parasite antibodies. In contrast, Th1-Tfh activation is not associated with antibody development but instead with plasma cells, which have previously been shown to play a detrimental role in the development of long-lived immunity. Thus, our study identifies the contrasting roles of Th2 and Th1-Tfh cells during experimental malaria.
CD4+滤泡辅助性 T 细胞（Tfh）是抗体产生的关键驱动因素。在儿童疟疾期间，Tfh 的激活仅限于 Th1 亚群，与抗体水平无关。为了鉴定与疟疾抗体产生相关的 Tfh 亚群，我们在人类志愿者中进行了实验性感染的 Tfh 和抗体的纵向评估。在感染过程中 Tfh 细胞被激活，不同 Tfh 亚群的动态不同。Th2-Tfh 细胞在感染高峰期早期激活，而 Th1-Tfh 细胞在感染高峰期后和治疗后 1 周激活。Th2-Tfh 细胞的激活与寄生虫抗体的功能广度和幅度有关。相比之下，Th1-Tfh 的激活与抗体的产生无关，而是与浆细胞有关，浆细胞以前被认为在产生长寿免疫方面起有害作用。因此，我们的研究鉴定了 Th2 和 Th1-Tfh 细胞在实验性疟疾中的对比作用。
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